Elastography-based screening for esophageal varices in patients with advanced chronic liver disease

Elastography-based liver stiffness measurement(LSM) is a non-invasive tool for estimating liver fibrosis but also provides an estimate for the severity of portal hypertension in patients with advanced chronic liver disease(ACLD). The presence of varices and especially of varices needing treatment(VNT) indicates distinct prognostic stages in patients with compensated ACLD(cACLD). The Baveno VI guidelines suggested a simple algorithm based on LSM < 20 kPa(by transient elastography, TE) and platelet count > 150 G/L for ruling-out VNT in patients with cACLD. These(and other) TE-based LSM cut-offs have been evaluated for VNT screening in different liver disease etiologies. Novel point shear-wave elastography(pSWE) and two-dimensional shear wave elastography(2D-SWE) methodologies for LSM have also been evaluated for their ability to screen for "any" varices and for VNT. Finally, the measurement of spleen stiffness(SSM) by elastography(mainly by pSWE and 2D-SWE) may represent another valuable screening tool for varices. Here, we summarize the current literature on elastography-based prediction of "any" varices and VNT. Finally,we have summarized the published LSM and SSM cut-offs in clinically useful scale cards.

Gut-liver axis signaling in portal hypertension

Portal hypertension(PHT)in advanced chronic liver disease(ACLD)results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition(structural component)and intrahepatic vasoconstriction(functional component).PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding.Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns(PAMPs)that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways.Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability:The intestinal barrier function is affected by impaired microcirculation,neoangiogenesis,and abnormal vascular and mucosal permeability.The close bidirectional relationship between the gut and the liver has been termed“gut-liver axis”.Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function,intestinal barrier integrity,as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects.The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments,however,further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed.In this review,we summarize the clinical impact of PHT on the course of liver disease,discuss the underlying pathophysiological link of PHT to gut-liver axis signaling,and provide insight into molecular mechanisms that may represent novel therapeutic targets.

Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis

Portal hypertension(PH),a common complication of liver cirrhosis,results in development of esophageal varices.When esophageal varices rupture,they cause significant upper gastrointestinal bleeding with mortality rates up to 20%despite state-of-the-art treatment.Thus,prophylactic measures are of utmost importance to improve outcomes of patients with PH.Several high-quality studies have demonstrated that non-selective beta blockers(NSBBs)or endoscopic band ligation(EBL)are effective for primary prophylaxis of variceal bleeding.In secondary prophylaxis,a combination of NSBB+EBL should be routinely used.Once esophageal varices develop and variceal bleeding occurs,standardized treatment algorithms should be followed to minimize bleeding-associated mortality.Special attention should be paid to avoidance of overtransfusion,early initiation of vasoconstrictive therapy,prophylactic antibiotics and early endoscopic therapy.Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding,and potentially in Child B patients with active bleeding at endoscopy.The use of carvedilol,safety of NSBBs in advanced cirrhosis(i.e.with refractory ascites)and assessment of hepatic venous pressure gradient response to NSBB is discussed.In the present review,we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.

Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease

The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease(MAFLD).While dyslipidemia,type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis,liver related morbidity and mortality becomes relevant for MAFLD’s progressive form,non-alcoholic steatohepatitis(NASH),and upon development of liver fibrosis.Statins should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world setting.Bariatric surgery,especially Y-Roux bypass,has been proven to be superior to conservative and/or medical treatment for weight loss and resolution of obesity-associated diseases,but comes at a low but existent risk of surgical complications,reoperations and very rarely,paradoxical progression of NASH.Once end-stage liver disease develops,obese patients benefit from liver transplantation(LT),but may be at increased risk of perioperative infectious complications.After LT,metabolic comorbidities are commonly observed,irrespective of the underlying liver disease,but MAFLD/NASH patients are at even higher risk of disease recurrence.Few studies with low patient numbers evaluated if,and when,bariatric surgery may be an option to avoid disease recurrence but more high-quality studies are needed to establish clear recommendations.In this review,we summarize the most recent literature on treatment options for MAFLD and NASH and highlight important considerations to tailor therapy to individual patient’s needs in light of their risk profile.